Fibrinogen degradation products (FDP) are usually found in blood as a result of disorders of the coagulation system. They are specifically an indication of a condition known as disseminated intravascular coagulation. They may also be implicated in impending myocardial infarction and the monitoring of their presence may be used as a tool to assess the progress of patients who have suffered from myocardial infarction. Further, their presence in the urine of patients who have received renal transplants is an indication that the transplant is being rejected.
At present there are a variety of tests and kits for analyzing the FDP content of serum and urine. Among such currently available are the following: (A) Staphylococcal Clumping Test -- Sigma Labs. Reference J. Hawiger, et al., J. Lab. Clin. Med., 75, 93 (1970). This test is based on the fact that a specific strain of Staphylococcus (Staphylococcus aureus Newman D.sub.2 C) will clump in the presence of monomeric fibrin or higher molecular weight FDP. Serial dilutions of samples are mixed with suspensions of the Staphylococcus cells on slides or in test tubes and the presence or absence of clumping noted. This test is non-immunologic in nature; (B) Fibrinogen Latex Test -- Hyland Labs. This is a direct latex agglutination slide test. Antibodies to human fibrinogen are coupled to latex particles. This test can be used for the detection of FDP because of immunological cross-reactivity but is somewhat lacking in sensitivity; (C) Hemagglutination-Inhibition Test -- ICL Scientific and Burroughs-Wellcome Co. Reference C. Merskey, et al., Proc. Soc. Exp. Biol. & Med., 131, 871 (1969). This is an indirect type of assay and as such is a two-step method. As generally performed, in the first step, dilutions of the test sample are incubated with a dilute solution of antibodies to human fibrinogen. In the second step, unreacted antibody (i.e. antibody not inhibited by FDP in the sample) is detected by adding tanned red blood cells coated with human plasma. If agglutination occurs no FDP was presented in the original sample dilution. If no agglutination occurs then the original sample contained sufficient FDP to neutralize the antibody. This technique is time consuming and requires extensive apparatus; and (D) Thrombo-Wellcotest -- Burroughs Wellcome Co. Reference P. M. Pitcher, Proc. Int. Soc. on Thrombosis and Haemostasis, Oslo, p. 282, 1971. (See U.S. Pat. No. 3,912,805.) This method is a direct latex agglutination test performed on a glass slide. The latex particles are coated with antibodies to D and E fragments which react directly with the FDP in the serum.
The above suffer from a varity of deficiencies, as for example the hemagglutination inhibition test (C) requires speciazlized apparatus, precise technique and is time consuming; the staphylococcus clumping test (A) is a non-immunological; test (B) is relatively less sensitive; and test (D) is subject to a high incidence of non-specific latex agglutination. With regard to test (D), Thromb. Research, 2, 23 (1970), reports that sera from 25% of patients with rheumatoid arthritis yielded non-specific agglutination and in testing urine the number of false positive rose to 50% even among healthy donors.
Diagnostic reagents formed by chemically coupling or combining a serologically determinant material to polymeric carrier particles of varying particle size, including latex particles, are well-known, e.g., U.S. Pat. Nos. 3,882,225; 3,857,931; 3,825,525; 3,639,558; 3,565,987; 3,553,310; 3,407,076; 3,236,732; and 3,096,250; Netherlands Pat. No. 7,201,308; and British Pat. No. 1,257,263. Latex particle-gamma globulin suspensions have been used in the serologic diagnosis of rheumatoid arthritis, Amerian Journal of Medicine 21; 888-892 (1956).